William L Macias
Affiliation: Eli Lilly and Company
- Protein C concentrations in severe sepsis: an early directional change in plasma levels predicts outcomeAndrew F Shorr
Department of Medicine, Section of Pulmonary and Critical Care Medicine, Washington Hospital Center, Washington, DC, USA
Crit Care 10:R92. 2006..The objective of this study was to determine whether early directional changes in protein C levels correlate with outcome...
- Lack of evidence for qualitative treatment by disease severity interactions in clinical studies of severe sepsisWilliam L Macias
Lilly Research Laboratories, Indianapolis, Indiana, USA
Crit Care 9:R607-22. 2005..Such an interaction might warrant a change in the assumptions that underlie current trial designs...
- Severe protein C deficiency predicts early death in severe sepsisWilliam L Macias
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
Crit Care Med 32:S223-8. 2004..To explore the relationship between measures of baseline disease severity and survival time in patients with severe sepsis...
- Relationship between exposure to prasugrel active metabolite and clinical outcomes in the TRITON-TIMI 38 substudyJeffrey S Riesmeyer
Eli Lilly and Company, Indianapolis, Indiana 46285, USA
J Clin Pharmacol 52:789-97. 2012....
- Sources of variability on the estimate of treatment effect in the PROWESS trial: implications for the design and conduct of future studies in severe sepsisWilliam L Macias
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA
Crit Care Med 32:2385-91. 2004..Diligence by coordinating centers, site investigators, study coordinators, and sponsors is necessary to ensure that the protocol is executed as designed such that a treatment benefit, if present, will be evident...
- The value of innovationWilliam L Macias
Lilly Research Laboratories, Indianapolis, USA
S Afr Med J 93:502-3. 2003
- New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated)William L Macias
Lilly Research Laboratories, Indianapolis, Indiana, USA
Crit Care 9:S38-45. 2005..This article discusses the way in which the interactions of APC may alter the microcirculation...
- Activated protein C and acute kidney injury: Selective targeting of PAR-1Akanksha Gupta
Lilly Research Laboratories, IN 46285 0444, USA
Curr Drug Targets 10:1212-26. 2009..The focus of this review will be to summarize the emerging data suggesting the potential therapeutic benefit of APC and related members of the pathway in the prevention and treatment of acute kidney injury...
- Pharmacokinetic-pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsisWilliam L Macias
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Ind 46285, USA
Clin Pharmacol Ther 72:391-402. 2002..We aimed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa (activated) (recombinant human activated protein C) in patients with severe sepsis...
- Population pharmacokinetic analyses to evaluate the influence of intrinsic and extrinsic factors on exposure of prasugrel active metabolite in TRITON-TIMI 38Rebecca E Wrishko
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
J Clin Pharmacol 49:984-98. 2009..1%) was 30% (90% confidence interval [CI] 1.16-1.45) higher than exposure in patients > or =60 kg. Mean Pras-AM exposures for patients > or =75 years (10.5%) were 19% (90% CI: 1.11-1.28) higher compared with patients <75 years...
- Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failureJean Francois Dhainaut
Department of Intensive Care, Cochin Hospital, AP HP, Cochin Institute, Cochin Port Royal Medical School, Paris V University, Paris, France
Crit Care Med 33:341-8. 2005..To determine whether changes in coagulation biomarkers during the first day of severe sepsis correlate with progression from single to multiple organ failure and subsequent death...
- Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsisE Wesley Ely
Division of Allergy, Pulmonary and Critical Care Medicine, Tennessee Valley Veteran s Affairs Geriatric Research Education and Clinical Center, Vanderbilt University School of Medicine, Nashville 37232 8300, USA
Crit Care Med 31:12-9. 2003....
- Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shockHector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
Am J Respir Crit Care Med 178:276-82. 2008..Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy...
- Elevated plasma concentrations of IL-6 and elevated APACHE II score predict acute kidney injury in patients with severe sepsisLakhmir S Chawla
Department of Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC 20037, USA
Clin J Am Soc Nephrol 2:22-30. 2007..IL-6 data and the absence of correlation with measures of hypotension (e.g., mean arterial pressure, dosage of vasopressors) support the notion that inflammation is a significant component of AKI in SS...
- Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated)Marcel Levi
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Am J Respir Crit Care Med 176:483-90. 2007..Biological plausibility exists for heparin to reduce DrotAA efficacy and/or increase bleeding...
- Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trialSimon Nadel
St Mary s Hospital and Imperial College, London, UK
Lancet 369:836-43. 2007..We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children...
- Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsisGordon R Bernard
Division of Allergy, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Crit Care 7:155-63. 2003....
- Activated protein C: do more survive?William L Macias
Intensive Care Med 32:605-7; author reply 610-2. 2006
- Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsisPhil Barton
Department of Pediatrics, Division of Pediatric Critical Care, Children's Hospital at Saint Francis, Tulsa, Oklahoma, USA
Pediatrics 113:7-17. 2004..A large, phase 3, randomized, placebo-controlled study is ongoing to confirm these results and formally assess the safety and efficacy of drotrecogin alfa (activated) in children...
- Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of deathEdward Abraham
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80262, USA
N Engl J Med 353:1332-41. 2005..The FDA required a study to evaluate the efficacy of DrotAA for adults who had severe sepsis and a low risk of death...
- Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic feverLisa E Hensley
Virology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA
J Infect Dis 196:S390-9. 2007..The aim of this study was to test the efficacy of rhAPC as a potential treatment for ZHF...
- A meta-analysis of controlled trials of anticoagulant therapies in patients with sepsisWilliam L Macias
Shock 20:582-3; author reply 583-4. 2003
- Early changes in organ function predict eventual survival in severe sepsisMitchell M Levy
Brown University School of Medicine, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
Crit Care Med 33:2194-201. 2005..We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to standard care should be significantly related to 28-day survival...